We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor beta (ERbeta) mRNA levels in tumor was tested. In males with low expression of ERbeta, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERbeta mRNA levels and in females. Accordingly, males with low expression of ERbeta and high expression of miR-30c showed a better survival that those with low expression ERbeta and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERbeta mRNA in tumor tissue.
- MeSH
- beta receptor estrogenů genetika metabolismus MeSH
- kohortové studie MeSH
- kolorektální nádory genetika metabolismus patologie MeSH
- lidé MeSH
- mikro RNA biosyntéza genetika MeSH
- míra přežití MeSH
- nádorové biomarkery biosyntéza genetika MeSH
- prognóza MeSH
- senioři MeSH
- sexuální faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The incidence of colorectal cancer (CRC) shows a sex-dependent difference in humans. The aim of this study was to analyze estrogen receptor beta mRNA (ERbeta) expression in patients with CRC with respect to their gender and clinicopathological features. Since cancer progression is accompanied by tumor vascularization, VEGF-A (vascular endothelial growth factor A) transcription was analyzed along with ERbeta mRNA. ERbeta mRNA was also correlated with the expression of clock genes, which are known to influence the cell cycle. ERbeta mRNA expression in females with CRC showed an inverse association with increasing tumor staging that was not observed in males. Lower levels of ERbeta mRNA were observed in females with a higher clinical stage compared with those with earlier-stage tumors. ERbeta mRNA expression showed a significant positive correlation with mRNA of clock genes period 2 and cryptochrome 2 in healthy but not in cancerous tissue in males. Expression of VEGF-A mRNA showed a negative correlation with ERbeta mRNA after splitting of the cohort according to gender and nodus involvement. We propose that gender differences in ERbeta mRNA expression in tumors during the early stages of CRC can partially explain the lower occurrence of CRC in females compared with males.
- MeSH
- beta receptor estrogenů metabolismus MeSH
- cirkadiánní rytmus - signální peptidy a proteiny metabolismus MeSH
- kohortové studie MeSH
- kolorektální nádory metabolismus MeSH
- lidé MeSH
- pohlavní dimorfismus * MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Suboptimal conditions during prenatal and early postnatal development can increase risk of hypertension later in life. We studied consequences of a changed perinatal environment by initiating the cross-fostering of homozygous Ren-2 transgenic rat (TGR) offspring to normotensive, transgene-negative control mothers, and vice versa. We hypothesized that cross-fostering to a normotensive female can attenuate the development of malignant hypertension in TGR offspring (TGRx) and change their salt-sensitive response. Blood pressure (BP) was monitored by the telemetry system under normal salt intake, and BP responses to increased salt intake in the phase of established hypertension. Under normal salt conditions, BP was not markedly different in cross-fostered animals compared with controls. However, BP responses to 2% salt intake led to a stronger BP response in TGRx during the active phase when compared with the control TGR group. The TGRx also exhibited increased albuminuria, lower sodium excretion, and creatinine clearance under higher salt intake compared with control salt intake. Higher salt intake resulted in a significant increase of aldosterone concentrations only in the TGRx group; moreover, TGRx rats exhibited more pronounced renal injury compared with controls. In conclusion, our data indicate that cross-fostering in TGR not only did not attenuate the development of hypertension but, on the contrary, led to the deterioration of BP regulation, particularly due to exaggerated salt sensitivity and sodium retention in TGRx. Results underline the important role of the mother during lactation in postnatal development of the offspring, since these changes reflected different ion content in milk of a particular strain of rats.
- MeSH
- aldosteron krev MeSH
- hypertenze genetika patofyziologie MeSH
- krevní tlak genetika fyziologie MeSH
- krysa rodu rattus MeSH
- ledviny patofyziologie MeSH
- potkani transgenní MeSH
- renin-angiotensin systém fyziologie MeSH
- renin genetika MeSH
- sodík dietní * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
miRNAs are small regulatory RNA molecules involved in posttranscriptional gene silencing. Their biosynthesis results in the formation of duplex consisting of a leading and a passenger strand of mature miRNA. The leading strand exhibits the main activity but recent findings indicate a certain role of the passenger strand as well. Deregulated levels of miRNA were found in many types of cancers including colorectal cancer. miR-21 and miR-16 were indicated as possible markers of colorectal cancer, however, small attention to gender differences in their expression was paid so far. Therefore, the aim of our study was to investigate the expression of miR-21-5p, miR-21-3p, miR-16-5p and miR-16-3p in human colorectal cancer tissue and compare it to the adjacent tissues taken during surgery in men and women separately. Our results showed an up-regulation of all measured miRNAs in tumor tissue compared to adjacent tissues. As expected, tumors and adjacent tissues exhibited a significantly higher expression of leading miRNAs compared to passenger strand of miR-21 and miR-16. The expression of leading and passenger strand of miR-21 and miR-16 positively correlated exhibiting the highest correlation coefficient in the distal tissue. The expression pattern showed gender-dependent differences, with higher levels of miRNA in men than in women. Our findings indicate a gender-related expression pattern of miRNA, which should be considered as an important factor in generating new prognostic or diagnostic biomarkers.
- MeSH
- kolon metabolismus patologie chirurgie MeSH
- kolorektální nádory metabolismus patologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA biosyntéza genetika MeSH
- pohlavní dimorfismus * MeSH
- regulace genové exprese u nádorů * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Disturbed circadian activity of the sympathetic system may be involved in negative consequences of chronodisruption on the cardiovascular system. We studied daily changes in pressure response to adrenergic stimulation in rats exposed to repeated phase advance shifts (PAS) of light/dark (LD) regimen. Blood pressure (BP), heart rate (HR) and locomotor activity was measured by radiotelemetry in normotensive Wistar rats exposed to repeated PAS (three 8-h shifts per week) lasting for 12 weeks. Norepinephrine was administered subcutaneously in the middle of L and D during week 12 of PAS exposure. In the control LD cycle, cardiovascular parameters exhibited significant daily rhythms with expected higher values during D than L phase. Rats exposed to PAS showed disturbed rhythms without a BP and HR increase. Administration of norepinephrine to control rats revealed daily variability in the cardiovascular response with higher stimulation of BP during L than D. This daily pattern of BP response to norepinephrine was diminished in the PAS group. The damped daily variability in pressure response to norepinephrine and augmented response during the light phase of the day suggest that the increased and desynchronized activity of the sympathetic system may worsen responses of the cardiovascular system to load in individuals exposed to irregular LD conditions.
- MeSH
- časové faktory MeSH
- cirkadiánní rytmus * MeSH
- fotoperioda * MeSH
- injekce subkutánní MeSH
- krevní tlak účinky léků MeSH
- noradrenalin aplikace a dávkování farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- srdeční frekvence účinky léků MeSH
- světlo * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH